The overall goal of this proposal is to study cytokine-mediated transcriptional regulation of the collagenase-3 (COLLASE-3 or Matrix Metalloproteinase 13 ([MMP 13]) gene. The COLLASE-3 gene is more specifically expressed in the skeletal system and has an additional cleavage site, which the other MMPs lack. Thus COLLASE-3 may play a more important role in cartilage breakdown, a significant feature in the pathophysiology of rheumatic diseases such a rheumatoid arthritis and osteoarthritis. The further understanding of the mechanisms of cartilage destruction that this work will provide may lead to development of novel therapeutic strategies.